A midbrain-thalamus-cortex circuit reorganizes cortical dynamics to initiate movement

Motor behaviors are often planned long before execution but only released after specific sensory events. Planning and execution are each associated with distinct patterns of motor cortex activity. Key questions are how these dynamic activity patterns are generated and how they relate to behavior. Here, we investigate the multi-regional neural circuits that link an auditory “Go cue” and the transition from planning to execution of directional licking. Ascending glutamatergic neurons in the midbrain reticular and pedunculopontine nuclei show short latency and phasic changes in spike rate that are selective for the Go cue. This signal is transmitted via the thalamus to the motor cortex, where it triggers a rapid reorganization of motor cortex state from planning-related activity to a motor command, which in turn drives appropriate movement. Our studies show how midbrain can control cortical dynamics via the thalamus for rapid and precise motor behavior

Protein phosphatase 2B dual function facilitates synaptic integrity and motor learning

Protein phosphatase 2B (PP2B) is critical for synaptic plasticity and learning, but the molecular mechanisms involved remain unclear. Here we identified different types of proteins that interact with PP2B, among which structural proteins of the postsynaptic densities (PSDs) of Purkinje cells (PCs) in mice of either se. Deleting PP2B reduced expression of PSD proteins and the relative thickness of PSD at parallel fiber to PC synapses, whereas re-expression of inactive PP2B partly restored the impaired distribution of nanoclusters of PSD proteins, together indicating a structural role of PP2B. In contrast, lateral mobility of surface glutamate receptors solely depended on PP2B phosphatase activity. Finally, the level of motor learning co-varied with both the enzymatic and non-enzymatic function of PP2B. Thus, PP2B controls synaptic function and learning both through its action as a phosphatase and as a structural protein facilitating synapse integrity.SIGNIFICANCE STATEMENTPhosphatases are generally considered to serve their critical role in learning and memory through their enzymatic operations. Here, we show that Protein Phosphatase 2B (PP2B) interacts with structural proteins at the synapses of cerebellar Purkinje cells. Differentially manipulating the enzymatic and structural domains of PP2B leads to different phenotypes in cerebellar learning. We propose that PP2B is crucial for cerebellar learning via two complementary actions, an enzymatic and a structural operation

Protein phosphatase 2b dual function facilitates synaptic integrity and motor learning

Protein phosphatase 2B (PP2B) is critical for synaptic plasticity and learning, but the molecular mechanisms involved remain unclear. Here we identified different types of proteins that interact with PP2B, including various structural proteins of the postsynaptic densities (PSDs) of Purkinje cells (PCs) in mice. Deleting PP2B reduced expression of PSD proteins and the relative thickness of PSD at the parallel fiber to PC synapses, whereas reexpression of inactive PP2B partly restored the impaired distribution of nanoclusters of PSD proteins, together indicating a structural role of PP2B. In contrast, lateral mobility of surface glutamate receptors solely depended on PP2B phosphatase activity. Finally, the level of motor learning covaried with both the enzymatic and nonenzymatic functions of PP2B. Thus, PP2B controls synaptic function and learning both through its action as a phosphatase and as a structural protein that facilitates synapse integrity.</p